BACKGROUND: Preeclampsia (PE) manifesting as hypertension and organ injury is mediated by vascular dysfunction. In biological fluids, extracellular vesicles (EVs) containing microRNA (miRNA), protein, and other cargo released from the placenta may serve as carriers to propagate injury, altering the functional phenotype of endothelial cells. PE has been consistently correlated with increased levels of placenta-derived EVs (pEVs) in maternal circulation. However, whether pEVs impaired endothelial cell function remains to be determined. In this study, we hypothesize that pEVs from pregnant women with severe PE (sPE) impair endothelial function through altered cell signaling. METHODS: We obtained plasma samples from women with sPE (n = 14) and normotensive pregnant women (n = 15) for the isolation of EVs. The total number of EV and pEV contribution was determined by quantifying immunoreactive EV-cluster of designation 63 (CD63) and placental alkaline phosphatase (PLAP) as placenta-specific markers, respectively. Vascular endothelial functional assays were determined by cell migration, electric cell-substrate impedance sensing in human aortic endothelial cells (HAECs), and wire myography in isolated blood vessels, preincubated with EVs from normotensive and sPE women. RESULTS: Plasma EV and pEV levels were increased in sPE when compared to normotensive without a significant size distribution difference in sPE (108.8 ± 30.2 nm) and normotensive-EVs (101.3 ± 20.3 nm). Impaired endothelial repair and proliferation, reduced endothelial barrier function, reduced endothelial-dependent vasorelaxation, and decreased nitrite level indicate that sPE-EVs induced vascular endothelial dysfunction. Moreover, sPE-EVs significantly downregulated endothelial nitric oxide synthase (eNOS and p-eNOS) when compared to normotensive-EV. CONCLUSIONS: EVs from sPE women impair endothelial-dependent vascular functions in vitro.
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Purpose of reviewThe aim of this review of cardiac disease in pregnancy is to delineate current best practices and highlight emerging themes in the literature. Recent findingsCardiovascular disease is the leading cause of death among pregnant women in the United States. Many clinicians and institutions have developed care pathways to approach care in these high-risk patients including highly coordinated multidisciplinary teams. The diagnosis of pulmonary hypertension is the greatest risk factor for an adverse event in pregnant women. Vaginal delivery, with good neuraxial anesthesia, is usually the preferred mode of delivery in women with cardiac disease, although the rate of cesarean delivery is higher among women with heart disease.
Background: We recently demonstrated that placenta-derived extracellular vesicles (pEVs) cargo play a role in vascular dysfunction in patients with severe preeclampsia (sPE). We focused our follow up studies on a novel protein vasorin (VASN) that has not as yet been studied in PE. Here, we hypothesize that decreased VASN in EVs cargo plays a significant role in the regulation of vascular endothelial proliferation and function in sPE. Methods: We manipulated VASN by overexpression and knockdown in human aortic endothelial cells (HAEC) and in murine aortic vascular rings (MVR) using adenoviral vectors encoding VASN (AD-VASN) or VASN shRNA (AD-shVASN), respectively. VASN levels in EVs, in HAEC and in MVR with/wo adenoviral overexpression or knockdown of VASN was done by western blotting. Migration of HAEC was studied by a scratch and repair migration assay and contractile function of MVR was assessed by wire myography. A PE-like vascular dysfunction was produced in timed pregnant mice by intravenous injection of an adenoviral vector encoding the short form of FMS-like tyrosine kinase 1 (sFLT-1) on embryonic day 10.5 (E10.5) of pregnancy. Plasma from sFLT-1 -injected and control untreated (UT) mice were collected on E15.5,E17.5 and E19.5. Results: We confirmed our findings with proteomics and using western blotting we detected a significant reduction in VASN levels in both urinary and plasma-derived EVs in sPE patients when compared to normotensive. Moreover, we detected a time-dependent significant reduction of VASN in EVs from plasma of sFLT-1 injected mice whereas UT mice exhibited a time-dependent increase of VASN. Western blotting also confirmed over-expression and knock down of VASN in HAEC and in MVR treated with AD-VASN and AD-shVASN, respectively. Treatment of HAEC with EVs from sPE, but not by EVs from NTP inhibited migration, and pretreatment with AD-VASN but not with AD-shVASN rescued migration upon treatment with EVs from PE. Treatment of MVR with EVs from sPE, but not by EVs from NTP inhibited acetylcholine (ACh)-induced vasorelaxation. Pretreatment with AD-VASN, but not with AD-shVASN rescued ACh-induced vasorelaxation upon treatment with EVs from sPE. Conclusion: Over-expression of VASN using adenoviral vectors rescued inhibitory effects of EVs from sPE on migration of HAEC and ACh-induced vasorelaxation in MVR, suggesting that reduced VASN content in EVs from sPE plays a mechanistic role in vascular dysfunction observed in sPE.
Neuraxial anesthesia is preferred over general anesthesia in obstetric patients to avoid airway manipulation, aspiration, and maternal-fetal transfer of medications; however, a sudden sympathetic block is generally avoided in patients with hypertrophic obstructive cardiomyopathy (HOCM). The case of a 31-year-old G2P0010 with HOCM with severe resting left ventricular outflow tract (LVOT) obstruction and systolic anterior motion of the mitral valve undergoing a cerclage under choroprocaine spinal anesthesia is presented. Risks and benefits of general versus neuraxial anesthesia, and epidural versus spinal anesthesia, in this specific setting are reviewed.
Differential diagnosis of the underlying cause of new-onset total body paralysis can be challenging and unsatisfying. In akinetic mutism, a rare side effect of tacrolimus, patients become apathetic, mute, and lose voluntary muscle movement. Epidural subarachnoid migration can present with similar symptoms. Delayed emergence/paralysis after anesthesia can include the common culprits of residual operative medications, stroke, as well as tacrolimus-induced akinetic mutism and thoracic epidural migration. We present a case of new-onset total body paralysis, presenting on postoperative day 1 following a double-lung transplant in a patient started on tacrolimus with a thoracic epidural catheter in place.
An intra-aortic balloon pump (IABP) may be placed preoperatively for high-risk patients with reduced ejection fraction or multivessel coronary disease undergoing non-cardiac surgery. Dexmedetomidine (DEX) has both anesthetic and cardioprotective effects, and little evidence is present on its effect on minimum alveolar concentration (MAC) and bispectral index (BIS). We present the case of a high-risk cardiac patient who was admitted and required fluid optimization prior to coronary artery bypass grafting (CABG). An IABP was placed after failure to tolerate intermittent hemodialysis (iHD). Bowel ischemia complicated this patient's course, necessitating an urgent exploratory laparotomy with the IABP in place. DEX and 0.3-MAC sevoflurane were successfully used without perioperative cardiac complications. Continuous BIS monitoring was performed to maintain an adequate level of anesthesia. DEX should be considered as an alternative anesthetic adjuvant in high-risk and medically complex patients.
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